Category: QA SOP

SOP Title: Temperature and Relative Humidity Mapping

1. Objective:

To lay down procedure for Temperature and Humidity Mapping in a room

2. Scope:

This procedure is applicable for the cubicle or room where Temperature and Relative Humidity is maintained and monitored within a specified limit in the site like Warehouse (General storage area, cold rooms), quarantine, Finished Goods Store and other storage area.

3. Responsibility:

QA Department- To prepare, review and approve procedure/protocol, conduct mapping study for cubicles/rooms/areas identified, prepare report, recommend necessary instructions and maintain records.

Concerned Department- To prepare/review procedure/protocol, assist in the mapping study, review mapping report and implement the recommendations in routine activity.

Engineering Department: To review protocol, assist in the mapping study with necessary technical support and review mapping report

4. Accountability:

Head QA/concerned Department

5. Procedure:

5.1  Definitions:

Mapping: Documented measurement of Temperature and Relative Humidity distribution within a storage area, including identification of hot and cold points.

Cold spot: A cold spot refers to the lowest temperature value(s) recorded in the space over the study period, but with these lowest temperature value(s) remaining within the specified temperature range.

Hot spot: A hot spot refers to the highest temperature value(s) recorded in the studied area over the study period, but with these highest temperature value(s) remaining within the specified temperature range.

Concerned Department: Department in which the mapping study is to be conducted.

QA Associate: Executive/officer of QA Department or any person trained to perform job as per this SOP.

5.2  Procedure:

5.2.1	Room/area which needs mapping in the site shall be identified based on the prospective use of the area or room.
5.2.2	Temperature and Humidity mapping shall be conducted by in-house personnel or external contractor as per approved procedure under normal operating condition.
5.2.3	A protocol for conducting temperature and humidity mapping shall be prepared by QA officer/executive which shall contain at least following contents: —Introduction —approval  sheet —objective —scope —responsibility —Documentation —procedure and acceptance criteria —Deviation —Summary report, conclusion and recommendations —annexure and attachments
5.2.4	The protocol shall be reviewed by authorized persons to ensure that all the aspects of mapping are mentioned logically with rationale and acceptance criteria
5.2.5	Protocol shall be approved prior to execution by authorized person
5.2.6	Issuance of approved protocol and report (blank) shall be for execution to the concerned department and retrieved as per SOP.
5.2.7	The temperature and RH measuring device used mapping must be calibrated before use and should have calibration error not more than ± 0.50C and ± 3 % RH at each calibration point. Valid calibration certificate for each device shall be included in the mapping report. Calibration temperature and RH points of each device should cover the range of area/room being studied.
5.2.8	A survey for the room/area to be mapped shall be conducted to collect necessary information e.g. dimensions, racks/shelves, location of heating/ cooling components, air distribution inlet/outlets, ceiling fans etc as applicable.
5.2.9	Acceptance criteria for temperature and RH shall be established depending on the storage conditioned of area/room designed as per product requirement as following table: Storage conditions and acceptance criteria Sr. No. Area/Room Storage condition Acceptance criteria Temperature (0C) RH (%) Temperature (0C) RH (%) 1. General storage area 15 – 25 40 – 60 ± 2 ± 5 2. Cold room 2 – 8 NA ± 2 NA 3. Low RH area Less than 20 or 10 – 20 10 – 40 ± 2 ± 2 4. Hot room 25 – 50 60 – 80 ± 2 ± 5
5.2.10	Locations for positioning of temperature and RH measuring device shall be identified as to be critical for temperature fluctuation within the room during storage, door opening etc. A map or drawing showing all locations with location ID/number shall be prepared as prescribed in Annexure and details shall be recorded as specified in Annexure. Minimum nine location shall be identified including each corner and one point in centre of the room. Generally one device shall be positioned at a distance of every 8 meters length in the room.
5.2.11	Temperature and RH device shall be positioned in the shelves or racks, directly above one another at high, medium and low level (for example sensor in a  room with ceiling height 3.6 meters shall be placed, one at floor level, one at 1.2 meters and one at 3.0 meters) if applicable.
5.2.12	Each measuring device shall be set with 30 minutes time interval for recording, labeled with location ID/number before positioning and recording shall be started at the same time for all devices for a period of 24 consecutive hours.
5.2.13	Make sure that each device is placed exactly as shown on the temperature device location map/drawing. Position and fasten the devices so that they cannot be damaged or displaced during the course of routine operations.
5.2.14	At the end of mapping duration all the devices shall be collected and double-checked for their location/ID Numbers.
5.2.15	The recording data shall be downloaded and consolidated in the computer as specified in Annexure and analysed for following parameters: —The ability of the environmental control systems to maintain temperatures and RH within the acceptance criteria limits (if any). —The overall temperature and RH stability of the area being monitored, and the range in fluctuations it experiences over the study period. —Variations experienced by individual device. —Temperature and RH variations along vertical and horizontal planes, depending on the size of the area, and distribution of devices. —Temperature variations in locations close to heating and cooling components, as compared to those farthest away from these units
5.2.16	From these data, the minimum and maximum temperature and RH that occur in the mapped area during the study period shall be identified as specified in Annexure  and hot and cold spot be specified.
5.2.17	Based on the observed temperature and RH fluctuations of mapped locations within the space, recommendations about the optimum storage locations for products/materials and optimum location of the temperature sensor(s) used for routine temperature monitoring shall be given to Concerned Department
5.2.18	The report contents shall include approval page, objective, scope, responsibility, procedure, acceptance criteria, deviation/change control if filed, mapping test data sheets, calibration certificates of measuring devices, training record of personnel conducting mapping, graphs, conclusion and recommendations and other necessary details of mapping study as applicable.
5.2.19	The mapping report shall be reviewed by the execution team for the complete data as prescribed in the protocol and should include at least points as mentioned in step 5.2.18.
5.2.20	Finally the mapping report shall be reviewed and approved by QA Department and shall be archived in QA Department
Frequency: 1- Mapping study shall be conducted at least twice (warmest and coldest season) to evaluate seasonal variation for new facility/room. Two seasons mapping study is not necessary for cold rooms and freezer rooms. 2- After three years from initial mapping study or after major change in the room that can influence the temperature and humidity condition whichever is earlier. 3- Mapping frequency for stability chamber, incubator, cooling chamber, oven refrigerator etc shall be done as per individual SOP.

 

6. Abbreviation:

Abbreviation	Expansion
SOP	Standard Operating Procedure
RH	Relative Humidity
ID	Identification
0C	Degree Celsius

 

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SOP Title: Receipt, Storage and Handling of Finished Products

1. Objective:

To ensure that the finished goods are received, stored and handled carefully and systematically so that their identity, traceability and security are preserved.  It also defines and implements the procedure for despatch of the finished goods.

2. Scope:

This procedure is applicable to Finished Products which are transferred from packing section.

3. Responsibility:

Warehouse Department: To receive, verify, store, monitor the Finished Product as per this procedure.

QA Department: To prepare & approve procedure and ensure the compliance of the procedure.

4. Accountability:

Head QA and Warehouse Department

5. Procedure:

5.1  Definitions:

Quarantine: The status of materials isolated physically or by other effective means while a decision is awaited on their release, rejection or disposal.

Finished product: A finished dosage form, for example a tablet, capsule or solution that contains an active pharmaceutical ingredient, generally but not necessarily, in association with inactive ingredients in a final marketed pack.

 

5.2  Procedure:

5.2.1	Receipt of Finished Products/Goods
5.2.1.1	On receipt of the Material transfer note in duplicate, the details of finished goods sent by Production Department shall be verified by comparing the actual stock against the details given in packed goods transfer note. The cases shall be examined for proper labelling, strapping and taping. Any discrepancy shall be brought to the notice of the Head of Quality Assurance for effective remedial action.
5.2.1.2	The finished goods received from Production Department should be kept in the ‘Quarantine’ area.
5.2.1.3	The Head Warehouse shall sign on the packed goods transfer note. The first copy shall be retained by the finished goods Warehouse, while second copy shall be returned to Production Department. Stock entry shall be made in the Material Control Record.   Both these entries shall be made on the date of receipt of the Finished Products.
5.2.1.4	The Finished Products shall be transferred to the approved finished goods area after getting Batch Release from QA and arranged batch-wise in a manner to facilitate easy access to each batch and to facilitate dispatch of every product on First In First Out (FIFO) basis.  Entry to the Warehouse Department shall be restricted and the stock shall be under the custody of Head Warehouse all the times.
5.2.2	Handling of Lorry Receipt and Invoice
5.2.2.1	A copy of the customer’s order / invoice will be signed by Head Warehouse as verification of despatch of the correct goods.  A copy of the delivery note will be attached to the order copy and sent to Accounts Department for invoicing.
5.2.3	Stock Posting
5.2.3.1	Based on the invoice the entries of the despatch of the goods shall be made in the Finished Goods Stock Register/Software.
5.2.4	Stock Statement
5.2.4.1	Fortnightly stock statement of Finished Products (sales) shall be prepared and signed. Any discrepancy shall be brought to the notice of responsible Person.  Copy of the Stock Statement shall be sent to the management.
5.2.5	Monthly Stock Statement
5.2.5.1	Monthly Stock Statement of Finished Products (sales) should be prepared within one week after closing of the month. Checking, verification and distribution of the statement shall be done as per step 5.2.4.
5.2.5.2	Physical stock verification of all products shall be done every month and the statement shall be signed confirming the correctness of the stock. Any discrepancy shall be brought to the notice of the responsible Person and Director.

 

6. Abbreviation:

QAP	Quality Assurance Procedure
FIFO	First In First Out

 

 

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SOP Title: Control of Artworks

1. Objective:

To lay down procedure for control of artwork preparation, approval, archival and issuance of artworks

2. Scope:

This procedure is applicable for the artworks of all products manufactured at the site.

3. Responsibility:

Quality Assurance Department: To prepare, review, approve and issue of artworks

Production Department: To review the artworks for correctness

Quality Control Department: To review and test the artwork

4. Accountability:

Head QA Department

5. Procedure:

• Definitions:

Artwork: Illustrative standard work prepared and approved for reproduction of finished products packaging components i.e. printed foil, cartons, package inserts, labels etc that is consist of drawing, painting, graphics or anything that is not typeset as only text and usually requires regulatory control as per the scope of this SOP.

• Procedure:

5.2.1	All finished products packaging components as applicable shall be provided with approved artworks which shall be maintained in QA Departments.
5.2.2	On receipt of the packaging details from the Marketing Department or contract giver, the cutter guide design for the carton shall be first made taking into account to check the suitability of packing, the text printing and pharmacode
5.2.3	The cutter guide drawing with dimensions is signed off by Head of Production and Quality Assurance and is then sent to the Marketing Department or customer for their approval.
5.2.4	On receipt of the signed off cutter guide by the Marketing Department / customer, the text matter and colour shall be incorporated onto the carton/packaging component.
5.2.5	The printer shall be asked to provide the wet proof of the carton design and shade cards light to dark colour (4 copies) which shall be circulated to the responsible persons (QC and Production Head) for review and comments (Wet proof are not required if the art works already exist and sourced from approved suppliers).
5.2.6	Once the artwork and the shade cards have been signed off by the respective persons listed in the artwork circulating form head QA shall sign off the final document for their approval.
5.2.7	In case the wet proof  or shade cards comes with corrections then the corrected version shall be resubmitted by the printer and which shall again be circulated to the responsible person giving the circulating document as revision 1, then revision 2 and so on till final correction of artwork
5.2.8	On receipt of the approved copies of the artwork and shade cards from the Marketing Department/customer (Contract giver), Head QA shall issue a copy to Purchase Department or intimate for initiating the printing.
5.2.9	Once the wet proof and shade cards approved by Marketing Department or customer (contract giver) then it shall be submitted to the customer to the relevant Regulatory Authority for their approval if required.
If the artwork of cartons are to be provided by the customer (wherever applicable & for exports) following procedure shall be followed:
5.2.10	Once the cutter guide has been approved the customer shall develop the artwork based on this cutter guide. The customer shall be asked to send the same on a CD or 4 hard copies of the signed off document.
5.2.11	The customer approved artwork on the CD shall be archived in QA Department and then be issued to Purchase Department for initiating the wet proof and shade cards. At this stage, item codes, pharmacodes and the product licence number shall be indicated on the hard copy and issued to the printer.
5.2.12	The wet proof and the shade cards (4 copies) light to dark colours, obtained from the printer shall be circulated to the responsible persons for review and comments.
5.2.13	Once the artwork and the shade cards have been signed off by the respective persons, Head QA shall sign off the final document for sending to the customer for their approval.
5.2.14	In case the wet proof and or shade cards requires corrections then the same shall be obtained from the printer with the corrected version and this version shall again be circulated to the responsible persons for review and comments giving the circulating document as revision 1, then revision 2 and so on till final correction of artwork.
5.2.15	Once the wet proof and shade cards approved by the customer (contract giver) then it shall be submitted by the customer to the relevant regulatory authority for their approval if warranted.
5.2.16	On receipt of the approved copies of the artwork and shade cards from the customer (Contract giver)/Regulatory authorities, a copy of the same shall be issued to Purchase Department for initiating the printing.
Artwork for package inserts and printed foil
5.2.17	The text for package insert and the printed foil shall be prepared and approved by QA Department after receiving the blister/strip layout details.
5.2.18	Once the text for the package insert and blister foil is received, it shall be send to the printer for development of wet proof and shade cards or a pdf file and the same is circulated to all responsible persons for review and comments.
5.2.19	If the wet proof and shade card requires any correction it shall be corrected by same procedure as mentioned in 5.2.14
5.2.20	The approved laser proof or wet proof and shade cards (if relevant) for foil and package insert is sent to the Marketing Department/customer for their comments and approval.
5.2.21	Once the wet proof and shade cards approved by the Marketing Department/customer (contract giver) then it shall be submitted by the customer to the relevant regulatory authority for their approval if warranted.
5.2.22	On receipt of the approved copies of the artwork and shade cards from the Marketing Department /customer (Contract giver)/Regulatory Authorities, head QA would issue a copy to Purchase Department for initiating the printing.
Labels
5.2.23	Same procedure shall be followed as mentioned in 5.2.17 to 5.2.22 for artwork approval of the labels.
5.2.24	The details on the carton/foil/label/tubes/inserts must be verified against the signed approved hard copy or pdf file from the customer.
5.2.25	Artwork Numbering System
5.2.26	Item code shall be considered as artwork number.
Issuance of artworks
5.2.27	All the approved artworks shall be kept in Quality Assurance Department. The controlled copy of the artwork/wet proof and shade cards to Regulatory, Marketing, Purchase Department, Production and Quality Control Department shall be issued whenever required.
5.2.28	Change in the artwork
5.2.29	In case of any change required in the current artworks, the artwork shall be reviewed only after raising a change control.
5.2.30	If required, the change control shall be approved by Marketing Department/ customer and Head QA Department
5.2.31	On approval of change control from, the Marketing Department/customer and head QA, the preparation of the new artwork shall be arranged together with Purchase Department following the procedure described as above.
5.2.32	New artwork number shall be assigned in the case of any change in the current artwork.
5.2.33	Revised artwork shall be submitted for regulatory approval if required, by the Marketing Department/customer.
5.2.34	Upon approval of revised artwork superseded copies of artwork shall be retrieved from Production, Regulatory, Quality Control and Purchase Department. In addition QC shall also return the specification relating to this particular. QA will only issue new approved copies on receipt of the superseded artwork.
Before approval of the new proof of the amended artwork, the following consideration shall be taken
5.2.35	The physical stock of existing printed packaging material shall be taken, also the quantity ordered by Purchase Department shall be considered.
5.2.36	The Marketing Department/customer shall be informed about the available stock of printed packaging material.
5.2.37	If the Marketing Department/customer prefers not to use the stock available, the existing stock shall be destroyed. The destruction shall be carried out in presence of QA person.
5.2.38	If the Marketing Department/customer prefers to consume the available stocks of printed packaging materials, then the wet proof shall be approved once the stocks gets consumed.
5.2.39	Once the change is implemented then QC Specification shall be revised the copy of revised specification shall be forwarded to Purchase Department.  The previous specification shall be superseded and withdrawn.

 

6. Abbreviation:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QAP	Quality Assurance Procedure
QA	Quality Assurance
CD	Compact Disk
QC	Quality Control

 

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SOP Title: Equipment/Instrument Calibration

1. Objective:

To control, calibrate and maintain inspection, measuring and test equipments.

2. Scope:

This procedure covers calibration of inspection, test and measuring equipments.

3. Responsibility:

Executive, Officer, Chemist – Quality Assurance

4. Accountability:

Head – QA/ Maintenance Head

5. Procedure:

5.1  Definitions:

Calibration: The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (for example, weight, temperature and pH), recording, and controlling, or the values represented by a material measure, and the corresponding known  values of a reference standard. Limits for acceptance of the results of measuring should be established.

Concerned Department:  Department in which the equipment or instrument is installed, operated and responsibility of calibration lies with.

 

5.2  Procedure:

5.2.1	A list of measuring instruments to be calibrated from out side approved calibration agencies shall be prepared for outside calibration.
5.2.2	Calibration Program: Calibration program shall include following aspects:
5.2.2.1	Equipment/instrumentation used in the manufacture, processing, testing, packaging, and warehousing/distribution of drug product shall be included in a calibration program where appropriate. Alarms, when functioning as the primary signal for identification of out of specification situations, must be periodically challenged at the measurement source.
5.2.2.2	Calibration schedules shall be identified for each type of instrument.
5.2.2.3	Written calibration procedures to describe calibration program shall include: —       Defined responsibilities. —       Established acceptance criteria. —       Range of use of instrument/equipment to include a minimum of three (3) point calibrations whenever feasible. —       Provisions for management notification of out of calibration result (OOC).
5.2.2.4	Provisions for investigation of out of calibration results shall include: —       Assessment of possible product impact. —       Corrective actions.
5.2.2.5	Identified calibration status of instrument/equipment.
5.2.2.6	Outside contractor calibration shall include: —        Written contract or procedure to define scope and responsibilities of contractor service. —        Calibration report reviewed and approved by authorized personnel.
5.2.3	All the identified instruments shall have an identification number clearly marked on them.
5.2.4	The status of calibration of measuring instruments shall be maintained.  All entries shall be checked and signed.
5.2.5	It shall be ensured that calibration is done as per relevant SOP at prescribed intervals and the records of calibration are maintained.

 

6. Abbreviation:

Abbreviation	Expansion
OOC	Out Of Calibration
SOP	Standard Operating Procedure
i.e.	Id Est (that is)
QAD	Quality Assurance Department

 

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SOP Title: Equipment & Machinery Maintenance

1. Objective:

To lay down procedure for preventive maintenance requirement and providing effective maintenance to machinery/equipments in the facility to ensure proper functioning.

2. Scope: This procedure is applicable to:

• Installation of new machinery and complete trial.
• Routine breakdown maintenance.
• Periodical preventive maintenance.
• Periodical servicing of the machinery/equipment.

3. Responsibility:

Head Concerned Department: Shall be responsible for identifying the requirement of maintenance as per schedule and compliance thereof.

Head Engineering: Shall be responsible for the timely execution of the maintenance and maintaining records thereof.

Plant Head: Shall be responsible for approval of the machinery and spares requirement and purchase thereof.

Head QA: Shall be responsible for preparing and approval of maintenance procedure and ensuring compliance thereof.

4. Accountability:

Head QA, Engineering and Concerned Department.

 

5. Procedure:

5.1  Definitions:

Preventive Maintenance: Preventative Maintenance is maintenance that is regularly performed on a piece of equipment to lessen the likelihood of it failing. Preventative maintenance is performed while the equipment is still working, so that it does not break down unexpectedly.

Breakdown Maintenance: Breakdown maintenance is maintenance performed on equipment that has broken down or proper working/operation stopped unexpectedly.

Concerned Department: Department in which the equipment or machinery is installed and operated and maintenance responsibility lies with.

5.2  Procedure:

5.2.1	Maintenance Program: Maintenance program shall include following aspects:
5.2.1.1	Equipment used in manufacturing, processing, testing, packaging and holding of drug product where applicable.
5.2.1.2	Provisions shall be made for notification to Concerned Department for maintenance schedule.
5.2.1.3	Maintenance operation should not compromise product quality.
5.2.1.4	Mechanism for production supervision to notify maintenance of potential problems.
5.2.1.5	Mechanism for Engineering to notify maintenance requirements/ spares to rectify/prevent potential problems.
5.2.1.6	Type of maintenance work required i.e. electrical, mechanical and civil.
5.2.2.	Maintenance Procedure
5.2.2.1	All machines shall be provided with Log Book, wherein the operational status of the machinery is recorded.
5.2.2.2	Whenever a breakdown occurs, a complaint note in complaint format shall be sent to the Engineering Department.
5.2.2.3	All general maintenance jobs shall be performed as per written procedure.
5.2.2.4	After completion of the maintenance job, the complainant shall sign the copy of the complaint note, in proof thereof.
5.2.2.5	If spares are required, proper indent shall be given to Stores (Maintenance).
5.2.2.6	Periodical maintenance and servicing of the machinery shall be done as per written procedure. Preventive maintenance schedule shall be prepared for all process equipment / machinery and records maintained, following written procedure.
5.2.2.7	Machines, which are under annual maintenance contract, shall be repaired by the concerned agency as specified in the list of approved service contractors.
5.2.2.8	Civil maintenance is done periodically under the supervision of Head Administration
5.2.2.9	Records for the repairs, servicing etc., as and when required, in the Machine Maintenance and Service Records.
5.2.2.10	All critical equipment including LAF, sampling and dispensing booths, balances, HVAC, boilers, RO-EDI water plant, dehumidifiers, stability chambers and compressors are maintained under annual service maintenance contract.

 

6. Abbreviation:

Abbreviation	Expansion
HVAC	Heating, Ventilation and Air Conditioning
LAF	Laminar Air Flow
i.e.	Id Est (that is)

 

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SOP Title: Product Recall Procedure

1. Objective:

To lay down procedure for recall of product which is found not to comply with the specification because of a defect in the products quality or because of a serious unexpected adverse drug reaction and withdrawn from the market immediately.

2. Scope:

The procedure sets out the chain of communications and responsibility for product recalls of all complaints related to the product from the market, practical recall process and how a recall is to be monitored and documented.

3. Responsibility:

Contract Giver	:	Shall be responsible for approval of the decision to be taken on the complaint received and recall of the product from market.
Contract Acceptor	:	Shall be responsible for recalling of the product from the market (if instructed by the Contract Giver).
Recall Committee	:	Recall Committee consist of Plant Head, Head of QA, Logistics Manager and Director.

4. Accountability:

Head Quality Assurance Department/Plant Head

5. Procedure:

5.1  Definitions:

Recall: The withdrawal from the market if a product is known or suspected to be defective.

Note:

1.   The recall procedure is expected to be completed within 30 days in case of domestic market.

2. The recall of product for the specific market shall be completed according to the regulatory norms of the respective country.
3. The recall may apply to a particular batch of the product or extend to a general prohibition against any use of the product in consequence of new information including a health risk to its consumers.
4. The recall shall only be made by Contract Acceptor when advised by Contract Giver.

5.2. Procedure: 

5.2.1	The Contract Giver shall advise and intimate for any product recall by email, fax or phone to the Contract Acceptor. The Head of QA shall pass it to the Recall Committee.  Details provided by phone must be followed-up by written confirmation.
5.2.2	Case Classification: Contract Giver shall recommend recall of the product under the following circumstances: Category-I : A situation in which there is a strong likelihood that the use of, or exposure to a product will cause serious adverse health consequences or death. Category-II: A situation in which use of, or exposure to a product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote. Category-III: Defect in quality of the product with respect to physicochemical characteristics, purity, efficacy. Category-IV: No threat to patients or serious defect likely to impair product efficacy. Category-V: Voluntary Recall.
5.2.3	Recall shall be initiated, but not limited to, the following circumstances: —Formulation problems, product mix-ups and other contaminants. —Label mix-ups and errors. —Physical and visual deterioration like significant discoloration, sedimentation, crystallization etc. —Drop in assay of active ingredients below the statutory limits. —Results of ongoing stability studies show significant changes in physiological   characteristics, purity, and microbial quality as prescribed in the specification. —Notification from API supplier of a defective material or batch of material.
5.2.4	The Recall Committee will conduct meeting to decide the following next steps: —Recall coordinator. —Recall action time limit. —Response to Contract Giver based on recall category. (Category I- within 24 hours, Category II-within 3 days, Category III-within 5 days, Category IV-within 7 days, Category V-within 15 days).
5.2.5	If the recall falls under category I, manufacturer shall take an immediate action for recall and simultaneously inform the Contract Giver and DMRC (Defective Medicines Report Centre).
5.2.6	If the recall is due to the defective API or batch of API, it shall immediately inform the same to the Contract Giver along with the information received from supplier to proceed for recall of the product.
5.2.7	The details of defective API will include: —Batch no of API. —Batch no of finished product & total batches affected. —Reason of failure.
5.2.8	Manufacturer shall also inform the DMRC regarding the defective API supply with details mentioned under Section 5.2.7.
5.2.9	A written status of product recall shall be forward to Director for approval with category to be mentioned.
5.2.10	Director shall approve recall decision.
5.2.11	If the product recall is approved, the same shall be intimated to the plant Head for recall operations.
5.2.12	The information shall be given to all Regulatory Authorities (local and of all countries to which products may have been distributed) if products have been decided to be recalled because they are suspected of being defective.  The DMRC (Defective Medicines Report Centre) shall be intimated for the action taken and updated with recall process.
5.2.13	Intimation to the Logistics Manager for the recall operations along with the product details shall be given.
5.2.14	Recall Documents
5.2.14.1	Manager (Logistics) shall ensure that an up to date list of all the emergency contact numbers and the product details are immediately available
5.2.14.2	The distribution records shall be readily available to the Manager (Logistics) for recalls, and shall contain sufficient information of wholesalers and directly supplied customers (with addresses, phone and/or fax numbers, inside and outside working hours, batches and amounts delivered), including those for exported products and medical samples.
5.2.14.3	Logistics Department shall assign a Recall number to each recalled product which shall be referred in all correspondence.
5.2.15	Public announcements
5.2.16	Logistics Department shall implement the required depth of recall of distribution from which a product is recalled, i.e. wholesale, retail, user/consumer and start the process by recall notification to accredited wholesalers/ Physicians/ Pharmacies/ Retails outlets/ Hospitals to return all unsold stock and get return feedback.  If required, product recall information shall be given on Media Network (Radio or, Television).
5.2.17	Recall Closeout
5.2.17.1	The Head of Marketing along with Logistics Manager shall ensure that all unsold stocks at all levels viz. stockist, distributors, retailers are immediately quarantined and returned to warehouses for further action.
5.2.17.2	All stocks of the recalled products at Warehouses shall be identified and stored separately in a secure area while awaiting a decision.
5.2.17.3	Complete reconciliation between the delivered and recovered quantities of the products shall be done as per Annexure  and forwarded to the Plant Head/Head QA for information.
5.2.17.4	A detailed investigation of the recalled batch shall be carried out and the reason for quality failure shall be evaluated and preventive action shall be initiated to avoid reoccurrence of such failure.
5.2.18	Mock Recall
5.2.18.1	A dummy recall exercise shall be conducted through the “Dummy Letter of Recall” as per Annexure once a year.  The dummy recall can be performed either by the Contract Giver or the Contract Acceptor in association with the Contract Giver, to cover up the entire chain of distribution.  The recall lead time along with percentage of goods recalled shall be recorded to ensure effectiveness of the procedure.
5.2.18.2	If the dummy recall exercise is carried out by the Contract Acceptor, then the Logistics Manager will inform the Contract Giver the details of the batch by telephone and the reason for recall and will email the recall form to the Contract Giver.
5.2.18.3	Contract Giver will than arrange to collect details of available stock at each distribution point and will intimate to the manager (logistics) of Contract Acceptor.
5.2.18.4	The details will be forwarded to the Recall Committee for review.
Note: The procedure shall be reviewed after every recall event and reviewed as necessary. This procedure shall not be applicable where recall advice is not received from Contract Giver. Contract Acceptor shall carryout the dummy recall only when the product is directly distributed by him to the distributors/ suppliers.

 

6. Abbreviation:

Abbreviation	Expansion
i.e.	Id Est.
API	Active Pharmaceutical Ingredient
DMRC	Defective Medicines Report Centre

 

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SOP Title: Product Manufacturing  Quality Plan

1. Objective:

To lay down procedure for systematic work plan for quality control of product manufacturing process to assure specified product quality attributes.

2. Scope:

This procedure is applicable to quality control plan for all stages of product manufacturing cycle i.e. RM/PM receipt, testing, storage, dispensing, batch manufacturing, packing and release.

3. Responsibility:

Concerned Department: Responsible to follow the procedure for operation and control material/product at each stage.

QA Department: Responsible to prepare, review and approve the procedure and ensure that the procedures and control points are being followed.

4. Accountability:

Head QA/All Department

5. Procedure:

• Definitions:
• QA Associate: Executive/officer or any person trained of Quality Assurance Department as per this SOP.
• Production Associate: Executive/officer or any person trained of Production Department as per this SOP.
• QC Associate: Executive officer of Quality Control Department or the personnel trained to perform duties as per this SOP.
• Warehouse Associate: Executive officer of Warehouse Department or the personnel trained to perform duties as per this SOP.
• Procedure:

5.2.1	All incoming materials shall be checked for physical damages, labelling and quantity requirements. Then the material shall be segregated as per the approved procedure, GRN & MCR of received material shall be sent to QC Department.
5.2.2	Based on the GRN & MCR received from warehouse inspection and sampling of incoming material shall be performed and material shall be labelled with yellow colour “UNDER TEST” label.
5.2.3	The sampled incoming material shall be  entered in the laboratory log book (separate for Raw & Packing materials), analyzed by Quality Control Analyst with IP, BP, EP,USP or In-house Specification.
5.2.4	The sample is analysed and all analysis results shall recorded in AWR (Analytical Work Record) log sheets and COA shall be prepared.
5.2.5	Based on AWR, a report Raw Materials and Packing Materials shall be labelled with green (APPROVED) label or red (REJECTED) label depends on the status.
5.2.6	A portion of API shall be retained as Control Sample as per approved procedure.
5.2.7	Only Approved Raw Materials shall be dispensed and used for manufacturing process.
5.2.8	Before start up of manufacturing process QA line clearance should be taken as per procedure to avoid contamination, cross-contamination and mix-up.
5.2.9	During each stage of manufacturing respective product BMR/BPR shall be available. All the manufacturing processes shall be carried with relevant BMR and BPR. Manufacturing process shall be carried out in direct supervision of competent technical staff.
5.2.10	During manufacturing initial and in-process checks shall be carried out as per product BMR/BPR.
5.2.11	All process materials in the processing area should be stored in specified closed container with proper labels.
5.2.12	Sampling of in-process product shall be carried and tested. After release of in-process bulk products, product shall be forwarded to further stage/activity.
5.2.13	Testing of bulk material shall be carried out as per product specification.
5.2.14	In case of any non-compliance, it shall be notified, investigated and corrected through proper documentation system.
5.2.15	The Finished Product is sampled and tested as per IP, BP, EP, USP & In-house specification
5.2.16	On analysis of the Finished Product, all data is recorded in Analytical work Record sheet.
5.2.17	A portion of the Finished Product is retained as ‘Control Sample/Retention Sample’ and record shall be maintained.
5.2.18	Based on the details of AWR, COA shall be prepared and copy shall be sent to QA.
5.2.19	The finally packed Finished Goods shall be inspected and a final inspection report is prepared.
5.2.20	The retained Control Samples are randomly checked for any physical changes and randomly batches are kept for stability.
5.2.21	All batch related records shall be retained for a minimum period one year after expiry of the product unless there is any regulatory commitment.
5.2.22	The Finished Product shall be inspected and released by the authorized person.

 

6. Abbreviation:

Abbreviation:	Expansion
QA	Quality Assurance
QC	Quality Control
BP	British Pharmacopoeia
EP	European Pharmacopoeia
USP	United State Pharmacopeia
IP	Indian Pharmacopoeia
AWR	Analytical Work Record
MCR	Material Control Record
GRN	Goods Receipts Note

           

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SOP Title: Emergency Power Failure

 

1. Objective

To lay down procedure for actions to be taken in case of emergency power failure during critical operations at the site

2. Scope:

This procedure is applicable to Production and Quality Control area

3. Responsibility:

Production Associate: To inform the incident to senior and follow the procedure

QA Associate: To verify, inform the incident to senior and follow the procedure

Engineering Associate: To verify, review, identify the cause of incident and take necessary actions

QC Associate: To inform the incident to senior and follow the procedure

4. Accountability:

Head QA/All head of departments

5. Procedure:

5.1  Definitions:

Emergency Power: Electricity temporarily produced and supplied by a standby power generator when the conventional electric power supply fails or is interrupted.

Emergency Power Failure: Failure of standby power generator to supply electric power which in turn causes the equipment to shut down.

 

5.2 Procedure

5.2.1	Actions to be taken during manufacturing of product (dispensing, granulation, compression ,blending, capsule filling, Packing etc) in Production Department in case of emergency power failure
5.2.1.1	Switch off the mains of machine and record the time of processing/activity or operation.
5.2.1.2	Remove or unload the material in proper manner in clean poly bag/container, tie/cover, label, segregate etc as applicable.
5.2.1.3	Inform immediate supervisor/department head.
5.2.1.4	Fill the ‘Complaint Note’ and submit to Engineering Department.
5.2.1.5	Fill the ‘Incident Report Form’ and submit to Quality Assurance Department.
5.2.1.6	Start further process/activity only after decision made through incident assessment.
5.2.1.7	After resumption of the power, check temperature, relative humidity and pressure differential of the area as per BMR/BPR.
5.2.1.8	Switch ON the main, check the equipment for correct operation, process parameter, product parameters etc.
5.2.1.9	Start further activity/operation/process for remaining time period to continue the process.
5.2.1.10	Record the details in the respective BMR/BPR and Equipment  Log.
5.2.2	Actions to be taken during testing operation of products (chemical, instrumental, microbiological etc) in Quality Control  Department in case of emergency power failure
5.2.2.1	Sophisticated equipment/instruments shall be provided with untripped power supply in the Quality Control laboratory.
5.2.2.2	For others switch off the mains of equipment/instrument and record the time of operation/activity in case of emergency power failure.
5.2.2.3	Inform immediate Supervisor/Department Head.
5.2.2.4	Fill the ‘Complaint Note’ and submit to Engineering department.
5.2.2.5	Fill the ‘Incident Report Form’ and submit to Quality Assurance Department.
5.2.2.6	Start  further testing operation/activity only after decision made through incident assessment based on impact on testing parameters.
5.2.2.7	After resumption of the power, check temperature, relative humidity and pressure differential of the area as applicable
5.2.2.8	Switch ON the main, check the equipment/instrument for correct operation, parameter etc.
5.2.2.9	Stabilise the solution for sample and continue the operation as per procedure.
5.2.2.10	Record the details in the respective worksheet and Instrument  Log
5.2.3	General Points:
5.2.3.1	An immediate decision shall be taken on the basis of impact assessment regarding further processing/activity of product to reduce risk to the product quality during emergency power failure.
5.2.3.2	Alternate equipment/processing step may be considered if applicable, through deviation when there is no significant impact product quality attributes.
5.2.3.3	Incident report should address comprehensive evaluation, analysis, investigation, action plan  and implementation with necessary recommendation to prevent such incident in future.
5.2.3.4	Specific assistance in investigation of root cause and corrective actions related to technical/mechanical or functional error or failure of standby power generator by external engineer or expert may be considered suitable as suggested by Engineering Head, if applicable.
5.2.3.5	A copy of incident report shall be attached to the respective product BMR/BPR after completion or closing of incident.
5.2.3.6	If the incident emergency power failure found frequent as a result of inefficient system/service for emergency power supply and/or modification or replacement of system is required, it should be brought to the notice of management for implementation of new efficient system.

6. Abbreviation:

 

Abbreviation	Expansion
QAP	Quality Assurance Procedure
HVAC	Heating Ventilation and Air Conditioning
BMR	Batch Manufacturing Record
BPR	Batch Packing Record
QAD	Quality Assurance Department
SOP	Standard Operating Procedure

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Batch coding system

1. Objective:

To define batch coding system for every batch of products manufactured at the site

2. Scope:

This procedure is applicable to all bulk and finished products manufactured at the site for following dosage forms:

2.1  Tablets

2.2  Capsules

2.3  Liquids

2.4 Creams and ointments

3. Responsibility:

Head QA	:	Overall responsibility for all product identification, batch coding and traceability in the manufacturing site as per procedure
Head Production	:	To ensure that all the products manufactured at the site are identified with their unique batch code as per this procedure

4. Accountability:

Head QA department

5. Procedure:

• Definition:

Batch Code: It is unique code given to identify each batch of the different product manufactured in the site as per this procedure.

Product Code: It is unique code given to each product manufactured in the site for identification and traceability as per this procedure.

 

• Procedure

5.2.1	Procedure of batch coding: Batches for each individual product shall be coded to clarify the following details: Dosage Forms Product identity code Year of manufacturing Serial no. of the batch. These categories are further elaborated and placed in a batch code no. as follows:
5.2.2	Dosage form:
5.2.2.1	The dosage form abbreviation of a product is the first alphabet taken from its dosage form and placed in first place in the batch Code No. / batch No. The following abbreviations shall be used for the different dosage form; T – Stands for the tablets C – Stands for the Capsules L – Stands for the Liquids O– Stands for Creams & ointments
5.2.3	Product identity code:
5.2.3.1	The product identity code shall be placed next to the dosage form abbreviation. It starts with two alphabets AA for first product of the a particular dosage form identified and reaches to AZ for others, further it starts with BA for twenty seventh product identified and so on for all products till ZZ.
5.2.4	Year of manufacturing:
5.2.4.1	The year of manufacture is taken as the numerical number from the last two digit of the current year such as for year 2024, the digit will be 24. The year of manufacture is placed next to the product identity code.
5.2.5	Serial number of batch:
5.2.5.1	The batch serial number is the numerical number between 001 to 999. The batch serial number is placed next to the year and consists of last 3 numerical numbers of any batch numbers. The serial number starts with 001 at the start of each year.
5.2.6	Example for a batch code number of different dosage forms
5.2.6.1	A typical batch code no. of first batch manufactured in year 2024 of different dosage forms  shall be assigned as following: Dosage form Product Code Batch code Batch code/batch number Tablets TAA 24001 TAA24001 Capsules CAA 24001 CAA24001 Liquids LAA 24001 LAA24001 Creams & Ointment OAA 24001 OAA24001

6. Abbreviation:

 

Abbreviation	Expansion
QA	Quality Assurance
QAD	Quality Assurance Department
QAP	Quality Assurance Procedure
No.	Number

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

Title: Vendor Evaluation and Approval

1. Objective:

To define procedure for Evaluation, Approval, Re-evaluation and Disqualification of Vendor/Supplier of Raw Materials, Primary and Printed Packaging Materials.

2. Scope:

This procedure is applicable to Vendors/Suppliers of all Raw Materials, Primary and Printed Packaging Materials.

3. Responsibility:

HOD (Planning & Purchase)	:	Sourcing the New Vendors and communication with vendors.
HOD (Production.)	:	Evaluating production related details and recommending suitable vendors.
Manager (Logistics)	:	Evaluating delivery performance and communicating to HOD (QA).
HOD (QA)	:	Evaluating the quality related details and vendor audit approval / re-approval of suitable vendors.

4. Accountability:

Head QA Department

5. Procedure:

5.1  Definitions:

Approved Vendors: A supplier or manufacturer or the combination of both which has been assessed and approved for a specific materials and included in approved vendor list.

5.2  Procedure :

5.2.1	The following inputs are required for vendor qualification: —Vendors are identified through personal references catalogues, trade journals, exhibitions, business directories and internet. — Particulars required for manufacturer / supplier capability evaluation (data received through audit or self assessment questionnaire and communication with the suppliers). — Sample inspection and test data. — Development batch production data. — Data of supplies. — Supplier audit data. — Supplier certificate of Analysis (COA).
5.2.2.	Raw Materials (Excipients)
5.2.2.1	Information about vendor background and capability shall be collected upon identification of a prospective source.
5.2.2.2	Specifications and vendor assessment form (questionnaire) shall be sent to supplier to evaluate the Quality Management System / GMP system implemented in the supplier premises.
5.2.2.3	If the vendor is only a dealer or supplier of manufacturer then it shall be ensured that the dealer or supplier is one of the authorized suppliers of the manufacturer.  Authorization letter from the manufacturer shall be sought in this regard.
5.2.2.4	It shall be ensured that the supplier provides the COA, filled assessment questionnaire and technical information about the required product/material along with the sample of 3 consecutive batches for QC evaluation purpose.  Without COA and filled assessment form (questionnaire), samples shall not be accepted.
5.2.2.5	It shall be ensured that COA of given product/material meets the relevant Pharmacopoeia/IH specification.
5.2.2.6	Criticality of the parameters mentioned in the supplier COA which could impact the quality of the product manufactured, shall be analysed jointly.
5.2.2.7	Received filled assessment form (Questionnaire) shall be reviewed for compliance and the comments shall be recorded.
5.2.2.8	Approval / rejection of the vendor shall be done on the basis of compliance of the raw material analysis on 100% sampling basis for the first 10 supplies or until the successful audit /assessment by manufacturer.
5.2.2.9	The supplier shall be ordered for supply of materials as per SOP.
5.2.2.10	Approved vendor list mentioning material code, material description, monograph / pharmacopoeial grade, material grade, manufactured for, manufacturer name with complete address, contact person, contact details and supplier name with complete address, contact person, contact details is prepared, updated, maintained and approved as specified in Annexure Copies of such approved vendor lists shall be made available to the warehouse and quality control department.
5.2.2.11	Continuous vendor evaluation shall be done on the basis of performance, quality, delivery etc. and shall be recorded.
5.2.2.12	If any non conformance observed in the materials or services, a letter shall be sent for review and tracking of corrective action to be taken by the supplier.
5.2.2.13	Validity period for all approved vendor/supplier shall be assigned as three years the date of inclusion in approved vendor/supplier list.
5.2.3	Raw Materials (API)
5.2.3.1	In addition to above procedures following additional steps shall be followed for approval of API vendor/supplier: — The vendor shall be audited by QA personnel or any other competent  authorized person prior to purchase of material for on spot assessment of particulars provided by them in vendor assessment form (questionnaire). — The manufacturer/supplier that has a valid GMP certificate, shall be selected, evaluated and approved.
5.2.4	Packing Materials
5.2.4.1	The primary and printed packing material (primary printed label, cartons and leaflets) vendor shall be approved on the basis of vendor assessment form (questionnaire) filled by vendors and on site audit (wherever possible).
5.2.4.2	The vendor/supplier shall be ordered to supply first ten supplies of the primary and printed packaging materials with COA and shall be completely tested to justify approval.
5.2.4.3	The supplies from approved vendors should be accompanied with a QC sample on the basis of decided criteria.
5.2.4.4	For secondary packing material supplier shall be asked for providing sample of materials and Assessment Questionnaire.
5.2.4.5	On the basis of quality of the sample and evaluation of assessment questionnaire, the vendor and supplies shall be approved.
5.2.5	Re-evaluation of vendor/suppliers
5.2.5.1	Monitor the performance rating half yearly to check the effectiveness of the vendor with quality and price for the supplied material as per criteria.
5.2.5.2	A vendor evaluation register (Quality performance rating record) shall be prepared from data collected of the respective vendors/supplier.
5.2.5.3	Re-evaluation of all vendors is done once in three years by QA Department on the basis of consistency in the quality of the supplied material and takes decision either to extend or stop the validity period of the supplier.
5.2.5.4	Where it is possible to take corrective action, it shall be communicated the same to the vendors otherwise be removed the vendor name from the approved list.
5.2.5.5	Manufacturer / suppliers for API shall be site audited once in three years for their continuing QMS. Assessment form questionnaire for suppliers are sent once in two year to evaluate the up gradation of their facility / system if any.
5.2.5.6	The supplier who was not issued purchase orders for a period of three years will get automatically removed from the approved vendor list.
5.2.5.7	In case if deleted suppliers are required to be enrolled once again for future supplies, they shall be undergone the specified evaluation and selection procedure.
5.2.5.8	The final recommendations shall be made which shall include following: —Re-approval based on re-evaluation particulars. —Inclusion of new supplier and the products approved for supply. —Needs of corrective action by the supplier. —Deletion of a supplier from approved list.
5.2.5.9	On the basis of above, the approved vendor list shall be updated as well as decisions communicated to the vendors.
5.2.6	Disqualification of suppliers
5.2.6.1	The vendors are disqualified on the basis of critical, major and minor categories: Critical: Any supply of the material rejected on quality grounds is termed as critical and vendor is disqualified and all purchases are suspended with immediate effect. Major: If the corrective action taken by the manufacturer is not satisfactory, then the vendor shall be disqualified. If the vendor does not meet the delivery date and delay is over 15 days or five consecutive supplies are delayed, the vendor shall be disqualified. Minor: If the corrective action is satisfactory, further procurement shall be carried out after onsite verification. If the supplies do not comply with one or two in-house physical parameters, then the vendor shall be disqualified.
5.2.6.2	The basis of vendor’s performance rating shall be as follows: PERFORMANCE: Performance evaluation shall be done on 0 to 2 scale and is based on his overall perception, which includes parameters like responsiveness, flexibility, cooperation, price, production/ supply capacity, etc.  This evaluation is done by head Planning & Purchase department. QUALITY: Done on 0 to 10 scale based on the quality of supplies.  Each consignment shall be given appropriate rating after inspection.  Rating of 10 shall be given in case if no shortcoming from QC.  In case of lot rejection, a rating of 0 shall be awarded. In between cases, including acceptance under concession, head QA shall provide approvals rating of 1 to 9. DELIVERY: Manager (Logistics) shall provide the date of delivery based on which information the Head QA shall rate the supplies on 0 to 3 scales.  If the supplies are within time, a rating of 3 shall be awarded; delay of upto 20 days attracts a rating of 2; 21-30 days – 1; over 1 month – 0. CALCULATION: Total rating of ‘Performance’, ‘Quality’ and ‘Delivery’ is obtained by adding the three. For quarterly average, sum of total ratings for supplies in a quarter is obtained and divided by the number of supplies received.
5.2.6.3	In case the quarterly average is below 6, a warning letter is sent to the vendor.  The party shall be continuously monitored for performance improvement.
5.2.6.4	In case the overall rating falls below 6, the party shall be blacklisted and all purchases from it shall be suspended.  In case of proprietary product / single source, the purchases may be continued with approval from the QA.
5.2.6.5	In case of disqualification, the vendor shall be informed the basis on which the disqualification was done.
5.2.6.6	The record of vendor qualification/disqualification shall be is maintained by QA Department

 

6. Abbreviation:

Abbreviation	Expansion
SOP	Standard Operating Procedure
GMP	Good Manufacturing Practices
HOD	Head of Department
COA	Certificate of Analysis
API	Active Pharmaceuticals Ingredients.
QMS	Quality Management System

 

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